{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:55:21Z","timestamp":1791816921476,"version":"4.3.4"},"reference-count":32,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"name":"Broxmeyer Fellowship in Clinical Thrombosis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hamostaseologie"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Limitations of vitamin K antagonists as chronic oral anticoagulant therapy have largely been supplanted by direct factor IIa and factor Xa inhibitor oral anticoagulants with similar efficacy but an overall better safety profile, lack of routine monitoring, and very limited drug\u2013drug interactions compared with agents such as warfarin. However, an increased risk of bleeding remains even with these new-generation oral anticoagulants in fragile patient populations, in patients requiring dual or triple antithrombotic therapy, or high bleed risk surgeries. Epidemiologic data in patients with hereditary factor XI deficiency and preclinical studies support the notion that factor XIa inhibitors have the ability to be an effective but potentially safer alternative to existing anticoagulants, based on their ability to prevent thrombosis directly within the intrinsic pathway without affecting hemostatic mechanisms. As such, various types of factor XIa inhibitors have been studied in early phase clinical studies, including inhibitors of the biosynthesis of factor XIa with antisense oligonucleotides or direct inhibitors of factor XIa using small peptidomimetic molecules, monoclonal antibodies, aptamers, or natural inhibitors. In this review, we discuss how different types of factor XIa inhibitors work and present findings from recently published Phase II clinical trials across multiple indications, including stroke prevention in atrial fibrillation, dual pathway inhibition with concurrent antiplatelets post\u2013myocardial infarction, and thromboprophylaxis of orthopaedic surgery patients. Finally, we refer to ongoing Phase III clinical trials of factor XIa inhibitors and their potential to provide definitive answers regarding their safety and efficacy in preventing thromboembolic events in specific patient groups.<\/jats:p>","DOI":"10.1055\/a-1984-7021","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T23:30:45Z","timestamp":1676935845000},"page":"028-036","source":"Crossref","is-referenced-by-count":23,"title":["A Review of FXIa Inhibition as a Novel Target for Anticoagulation"],"prefix":"10.1055","volume":"43","author":[{"given":"Ioannis","family":"Koulas","sequence":"additional","affiliation":[{"name":"The Institute of Health Systems Science at the Feinstein Institutes for Medical Research, Manhasset, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex C.","family":"Spyropoulos","sequence":"additional","affiliation":[{"name":"The Institute of Health Systems Science at the Feinstein Institutes for Medical Research, Manhasset, New York, United States"},{"name":"Northwell Health at Lenox Hill Hospital, New York, New York, United States"},{"name":"The Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1055\/a-1384-3715","article-title":"Factor XI as a target for new anticoagulants","volume":"41","author":"J C Fredenburgh","year":"2021","journal-title":"Hamostaseologie"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/jth.15126","article-title":"New anticoagulants: moving beyond the direct oral anticoagulants","volume":"19","author":"J C Fredenburgh","year":"2021","journal-title":"J Thromb 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Georgi","year":"2019","journal-title":"Stroke"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1309\/QC259F09UNMKVP0R","article-title":"Elevated factor XI activity levels are associated with an increased odds ratio for cerebrovascular events","volume":"126","author":"D T Yang","year":"2006","journal-title":"Am J Clin Pathol"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1056\/NEJM200003093421004","article-title":"High levels of coagulation factor XI as a risk factor for venous thrombosis","volume":"342","author":"J C Meijers","year":"2000","journal-title":"N Engl J Med"},{"issue":"06","key":"ref11","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1055\/s-0033-1353420","article-title":"Congenital factor XI deficiency: an update","volume":"39","author":"S Duga","year":"2013","journal-title":"Semin Thromb 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Rao","year":"2022","journal-title":"Circulation"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/S0140-6736(22)01588-4","article-title":"Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial","volume":"400","author":"A Shoamanesh","year":"2022","journal-title":"Lancet"},{"issue":"10","key":"ref19","doi-asserted-by":"crossref","first-page":"106742","DOI":"10.1016\/j.jstrokecerebrovasdis.2022.106742","article-title":"Rationale and design of the AXIOMATIC-SSP phase II trial: antithrombotic treatment with factor XIa inhibition to optimize management of acute thromboembolic events for secondary stroke prevention","volume":"31","author":"M Sharma","year":"2022","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1182\/blood.V118.21.209.209","article-title":"ISIS-FXIRx, a 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